It is generally agreed that estrogens, principally estradiol-17beta, are synthesized by and act in the testis of mammals, including humans. The site of estradiol synthesis in the testis is generally believed to begin in the Sertoli cell and switch to the Leydig cell during neonatal development where a gonadotropin-regulated aromatase is present. Numerous studies suggest that the primary target cell of estradiol in the testis at all ages is the Leydig cell. In fact, the Leydig cell is known to possess an estrogen receptor that binds estradiol in the classic manner. The mechanism of estradiol action and the role of its receptor in the testis, however, remain unresolved. In Leydig cells, estradiol appears to induce several alterations that are dependent in large part on the developmental stage of the Leydig cell. In the fetal and neonatal testes, estradiol appears to block the ontogenic development of Leydig cells from precursor cells. There is also evidence that estradiol similarly blocks the regeneration of Leydig cells in the testis of mature, ethane dimethylsulfonate-treated animals. Evidence indicates that the precursor cell possesses high levels of estrogen receptors relative to that of the Leydig cell. It is postulated that estradiol is a paracrine factor involved in regulating the interstitial population of Leydig cells. Evidence also indicates that estradiol acts directly in the mature testis to block androgen production. It appears to do so by inhibiting the activities of several steroidogenic enzymes involved in testosterone synthesis. Although the more conventional receptor-mediated mode of action is feasible, several studies have suggested that this action might entail direct competitive inhibition of key steroidogenic enzymes by estradiol. In summary, the net biologic effect of estradiol in the testis appears to be inhibition of androgen production, either by limiting development and growth of the Leydig cell population or through direct action in the Leydig cell.